Review
Oncology
Mercedes Herrera-Juarez, Cristina Serrano-Gomez, Helena Bote-de-Cabo, Luis Paz-Ares
Summary: Precision oncology aims to design the best cancer treatment based on tumor biology. In NSCLC, patients with actionable genomic aberrations can benefit from targeted therapy, such as EGFR mutations and ALK rearrangements. Effective inhibitors have been developed for various druggable targets, leading to a paradigm shift in NSCLC treatment.
Article
Oncology
Yaping Zhang, Hui Wang, Xiaoyan Wang, Shuai Li, Hongming Fang
Summary: EGFR, ALK, and ROS1 mutations are typically considered mutually exclusive. This article describes a rare case of a patient with triple mutations in EGFR, ALK, and ROS1 in advanced NSCLC, who responded well to multiple treatment options with a slightly poorer overall survival than patients with single driver gene mutations.
CLINICAL LUNG CANCER
(2021)
Article
Oncology
Luis D. Borrero-Garcia, Maria del Mar Maldonado, Julia Medina-Velazquez, Angel L. Troche-Torres, Luis Velazquez, Nilmary Grafals-Ruiz, Suranganie Dharmawardhane
Summary: Despite the availability of targeted therapies for cancers expressing oncogenic EGFR and HER2, resistance to therapy remains a challenge. In a study on breast cancer cells, gefitinib and lapatinib resistant variants exhibited enhanced mesenchymal and cancer stem cell-like characteristics, along with increased expression and activation of the small GTPase Rac, suggesting Rac inhibition as a potential strategy to overcome therapy resistance.
Review
Chemistry, Medicinal
Adileh Ayati, Setareh Moghimi, Mahsa Toolabi, Alireza Foroumadi
Summary: Despite advancements in cancer treatment, EGFR inhibitors have shown significant improvement in targeted therapy. However, the emergence of epigenetic mutation and resistance issues have limited their effectiveness, leading to the need for further research in this field. Recent studies have focused on genetic alterations in the EGFR tyrosine kinase domain, resulting in the development of more selective and effective inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ahlem Jebali, Maxime Battistella, Celeste Lebbe, Nicolas Dumaz
Summary: The network involving PI3K, AKT, and mTOR is important in melanoma oncogenesis, with RICTOR overexpression associated with poor prognosis. RICTOR enhances melanoma-initiating cells with stemness properties and contributes to resistance to BRAF inhibitors. An interaction between RICTOR and STAT3 in resistant cells, as well as a connection between RAS and RICTOR in resistant melanoma, were identified, suggesting RICTOR as a valuable therapeutic target in melanoma.
Review
Oncology
Maria San Roman-Gil, Javier Pozas, Diana Rosero-Rodriguez, Jesus Chamorro-Perez, Alvaro Ruiz-Granados, Ignacio Ruz Caracuel, Enrique Grande, Javier Molina-Cerrillo, Teresa Alonso-Gordoa
Summary: Thyroid cancer is a common endocrine malignancy with increasing incidence. Recent advances in understanding the molecular mechanisms of thyroid cancer have improved treatment approaches. Selective RET inhibitors have shown promising results in selected patients, but resistance mechanisms have been observed. This review provides an analysis of resistance mechanisms to RET inhibitors, aiming to inform the development of next-generation therapies and combination strategies.
CANCER TREATMENT REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Siming Liu, Chuan Huang, Chunhui Huang, Yaqi Huang, Yonghuan Yu, Guowu Wu, Fengqiu Guo, Ying Jiang, Shanhe Wan, Zhengguang Zhu, Yuanxin Tian, Jianghua Zhu, Jiajie Zhang
Summary: Clinical treatment with the FDA-approved ROS1/ALK inhibitor Crizotinib has significantly improved therapeutic outcomes. However, drug resistance, especially due to acquired mutations, has become a problem and reduced the efficacy of Crizotinib. To address this issue, novel 2-aminopyridine derivatives were designed, synthesized, and tested. The spiro derivative C01 showed remarkable activity against drug-resistant mutants and had higher potency than Crizotinib. These findings suggest the potential for developing anti-Crizotinib-resistant dual inhibitors for ROS1/ALK.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Rimma S. Mulkidjan, Evgeniya S. Saitova, Elena V. Preobrazhenskaya, Karimat A. Asadulaeva, Mikhail G. Bubnov, Ekaterina A. Otradnova, Darya M. Terina, Sofia S. Shulga, Darya E. Martynenko, Maria V. Semina, Evgeniya V. Belogubova, Vladislav I. Tiurin, Priscilla S. Amankwah, Aleksandr S. Martianov, Evgeny N. Imyanitov
Summary: This study conducted a comprehensive analysis of gene rearrangements in tumors with microsatellite instability (MSI). Gene fusions were detected in colorectal carcinomas (CRCs), gastric cancers (GCs), and endometrial cancers (ECs), but not in cervical carcinomas (CCs), pancreatic cancers (PanCs), cholangiocarcinomas (ChCs), and ovarian cancers (OCs). The frequency of gene rearrangements was highest in KRAS/NRAS/BRAF wild-type CRCs. There was a higher frequency of translocations in CRC patients aged above 50 years, particularly in tumors with normal KRAS/NRAS/BRAF status.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Anna Wrona, Rafal Dziadziuszko, Jacek Jassem
Summary: Combining radiotherapy with targeted agents in non-small cell lung cancer (NSCLC) holds promise for improving treatment outcomes, but so far, no targeted agent has shown clear clinical benefit over standard chemoradiation in locally advanced NSCLC. Well-designed clinical trials may help develop more effective combination strategies.
TRANSLATIONAL LUNG CANCER RESEARCH
(2021)
Article
Oncology
Stephanie G. C. Kroeze, Corinna Fritz, Jana Schaule, Oliver Blanck, Klaus Henning Kahl, David Kaul, Shankar Siva, Sabine Gerum, An Claes, Nora Sundahl, Sonja Adebahr, Susanne Stera, Markus M. Schymalla, Nasrin Abbasi-Senger, Daniel Buergy, Michael Geier, Marcella Szuecs, Fabian Lohaus, Guido Henke, Stephanie E. Combs, Matthias Guckenberger
Summary: The study analyzed the safety and efficacy of combining SRT with TT in metastatic cancer patients, finding that interrupting TT during SRT did not significantly affect patient survival or progression. Although some acute and late toxicity related to SRT was observed, severe toxicity rates were low overall. More research is needed to evaluate potential increased toxicity with continuous treatment of EGFR inhibitors or BRAF/MEK inhibitors after SRT in these patients.
Article
Oncology
Giorgia Nardo, Jessica Carlet, Ludovica Marra, Laura Bonanno, Alice Boscolo, Alessandro Dal Maso, Andrea Boscolo Bragadin, Stefano Indraccolo, Elisabetta Zulato
Summary: The study found that co-existing KRAS mutations in EGFR mutated NSCLC patients at progression after first-line EGFR TKI treatment are rare, and they have a negative impact on the response to EGFR TKI.
FRONTIERS IN ONCOLOGY
(2021)
Review
Chemistry, Medicinal
Yingxue Li, Yanna Lv, Cheng Zhang, Binyu Fu, Yue Liu, Jinxing Hu
Summary: As a member of the insulin-receptor superfamily, ALK plays a vital role in regulating cell growth, proliferation, and survival. ROS1, highly similar to ALK, also regulates normal physiological activities of cells. Overexpression of both is closely associated with tumor development and metastasis, making ALK and ROS1 important therapeutic targets in NSCLC. While many ALK inhibitors have shown significant therapeutic efficacy in ALK and ROS1-positive NSCLC patients, drug resistance eventually develops, leading to treatment failure. This review summarizes the chemical structural features of novel dual ALK/ROS1 inhibitors, their inhibitory effect on ALK and ROS1 kinases, and future treatment strategies for patients with ALK and ROS1 inhibitor-resistant mutations.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Aleksandr S. Martianov, Natalia V. Mitiushkina, Anastasia N. Ershova, Darya E. Martynenko, Mikhail G. Bubnov, Priscilla Amankwah, Grigory A. Yanus, Svetlana N. Aleksakhina, Vladislav I. Tiurin, Aigul R. Venina, Aleksandra A. Anuskina, Yuliy A. Gorgul, Anna D. Shestakova, Mikhail A. Maidin, Alexey M. Belyaev, Liliya S. Baboshkina, Aglaya G. Iyevleva, Evgeny N. Imyanitov
Summary: This study analyzed the factors influencing the distribution of actionable genetic alterations in colorectal carcinomas. The study found that there were differences in the distribution of certain genetic alterations based on patients' age and gender. BRAF mutation frequency also showed geographic variation. In addition, a small fraction of CRCs had simultaneous alterations in more than one driver gene.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Nanoscience & Nanotechnology
Ayimukedisi Yalikong, Xu-Quan Li, Ping-Hong Zhou, Zhi-Peng Qi, Bing Li, Shi-Lun Cai, Yun-Shi Zhong
Summary: The HER2-targeted nanoparticles (TPLNP) drug delivery system has shown significant anti-tumor effects on colon cancer with HER2 overexpression and BRAF mutation in preclinical models, suggesting promising potential for clinical application.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2021)
Review
Oncology
Maria Florencia Mercogliano, Sofia Bruni, Florencia Luciana Mauro, Roxana Schillaci
Summary: Breast cancer is a common and deadly disease, with HER2 overexpression being associated with a poor prognosis. While trastuzumab is the standard treatment, many patients do not respond to it. Other HER2-targeted therapies, such as pertuzumab, margetuximab, and T-DM1, as well as tyrosine kinase inhibitors, have been developed. Combination therapies with immune checkpoint inhibitors, CAR-T cells, CAR-NK cells, CAR-M cells, and vaccines are also being explored. This review discusses the different HER2-targeted therapies and potential combinations to overcome resistance.
Review
Critical Care Medicine
Ayushi F. Chauhan, Stephen V. Liu
SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE
(2020)
Review
Oncology
Sushma Jonna, Joshua E. Reuss, Chul Kim, Stephen V. Liu
FRONTIERS IN ONCOLOGY
(2020)
Article
Oncology
Jacques Cadranel, Stephen V. Liu, Michael Duruisseaux, Eva Branden, Yasushi Goto, Benjamin A. Weinberg, Christoph Heining, Richard F. Schlenk, Parneet Cheema, Martin R. Jones, Alexander Drilon, Domenico Trombetta, Lucia Anna Muscarella, Khaled Tolba, Valerie Gounant, Agnieszka Cseh, Flavio Solca, Janessa J. Laskin, Daniel J. Renouf
Summary: Neuregulin 1 (NRG1) fusions, rare oncogenic drivers in multiple tumor types, can be effectively treated with afatinib, a pan-ErbB family inhibitor. This report summarizes six cases of metastatic NRG1 fusion-driven tumors treated with afatinib, with several patients showing a prolonged response of >18 months.
Article
Oncology
Adriana Estrada-Bernal, Anh T. Le, Andrea E. Doak, Vijaya G. Tirunagaru, Shevan Silva, Matthew R. Bull, Jeff B. Smaill, Adam V. Patterson, Chul Kim, Stephen V. Liu, Robert C. Doebele
Summary: Tarloxotinib, a prodrug that utilizes tumor hypoxia to generate a potent pan-HER tyrosine kinase inhibitor, demonstrated selective delivery to tumor cells and effective inhibition of EGFR exon 20, ERBB2 mutations, and NRG1 fusions in cancer models. The concentrated presence of tarloxotinib-E in tumor tissues led to tumor regression and growth inhibition in mouse xenografts, with promising clinical responses observed in patients with relevant mutations.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Stephen Liu, Martin Reck, Aaron S. Mansfield, Tony Mok, Arnaud Scherpereel, Niels Reinmuth, Marina Chiara Garassino, Javier De Castro Carpeno, Raffaele Califano, Makoto Nishio, Francisco Orlandi, Jorge Alatorre-Alexander, Ticiana Leal, Ying Cheng, Jong-Seok Lee, Sivuonthanh Lam, Mark McCleland, Yu Deng, See Phan, Leora Horn
Summary: IMpower133 trial showed that adding atezolizumab to CP/ET for first-line treatment of ES-SCLC significantly improved patients' overall survival. Atezolizumab demonstrated potential efficacy in treating ES-SCLC.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Rafal Dziadziuszko, Matthew G. Krebs, Filippo De Braud, Salvatore Siena, Alexander Drilon, Robert C. Doebele, Manish R. Patel, Byoung Chul Cho, Stephen V. Liu, Myung-Ju Ahn, Chao-Hua Chiu, Anna F. Farago, Chia-Chi Lin, Christos S. Karapetis, Yu-Chung Li, Bann-mo Day, David Chen, Timothy R. Wilson, Fabrice Barlesi
Summary: Entrectinib continues to show a high level of clinical benefit for patients with ROS1 fusion-positive NSCLC, including those with central nervous system metastases.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Elizabeth Dudnik, Samuel Kareff, Mor Moskovitz, Chul Kim, Stephen Liu, Anastasiya Lobachov, Teodor Gottfried, Damien Urban, Alona Zer, Ofer Rotem, Amir Onn, Mira Wollner, Jair Bar
Summary: This study of 125 patients suggests a positive impact of ICI on overall survival in aLCNEC, despite the limitations of retrospective design and small sample size.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Oncology
Diego Cortinovis, Paolo Bidoli, Stefania Canova, Francesca Colonese, Maria Gemelli, Maria Luisa Lavitrano, Giuseppe Luigi Banna, Stephen V. Liu, Alessandro Morabito
Summary: Small cell lung cancer is a deadly subtype of lung cancer with fast doubling time and early metastasis. Traditional chemotherapy regimens have shown high response rates, but early chemoresistance leads to poor prognosis in advanced cases. Only a few patients with limited disease can be cured through chemo-radiotherapy, and the development of novel chemotherapy agents is eagerly awaited due to disappointing survival rates in advanced stages.
Article
Oncology
Stephen V. Liu
Summary: NRG1 fusions are rare oncogenic drivers found at low frequencies across multiple tumor types, with an estimated incidence of 0.2% in lung cancer. Despite challenges in detection due to large intronic regions, NRG1 fusions represent potential therapeutic targets. Early evidence of efficacy has been shown for agents targeting the ErbB signaling pathway, with limited supporting data mostly from case reports and small series, but prospective trials are ongoing. The evolving understanding suggests that NRG1 will be clinically relevant in the future.
Review
Oncology
Joshua E. Reuss, Laura Gosa, Stephen Liu
Summary: ADCs combine the specificity of a monoclonal antibody with the cytotoxic effects of chemotherapy to facilitate targeted delivery of cytotoxic payloads to cancer cells. ADCs show promise in lung cancer treatment, with future applications looking increasingly relevant.
CLINICAL LUNG CANCER
(2021)
Article
Oncology
George D. Demetri, Filippo De Braud, Alexander Drilon, Salvatore Siena, Manish R. Patel, Byoung Chul Cho, Stephen Liu, Myung-Ju Ahn, Chao-Hua Chiu, Jessica J. Lin, Koichi Goto, Jeeyun Lee, Lyudmila Bazhenova, Thomas John, Marwan Fakih, Sant P. Chawla, Rafal Dziadziuszko, Takashi Seto, Sebastian Heinzmann, Bethany Pitcher, David Chen, Timothy R. Wilson, Christian Rolfo
Summary: This study provides additional evidence on the safety and efficacy of Entrectinib in treating NTRK fusion-positive solid tumors, with prolonged follow-up and an increased number of patients.
CLINICAL CANCER RESEARCH
(2022)
Editorial Material
Oncology
Charu Aggarwal, Stephen V. Liu
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Stephen V. Liu, Ivy B. Elkins, Jill Feldman, Sarah B. Goldberg
Summary: This podcast discusses the importance of biomarker testing for patients with EGFR-mutated non-small cell lung cancer, including the definition of biomarkers, the process of obtaining biomarker testing, and the significance of waiting for biomarker results before determining treatment. The panel also explores patient perspectives on biopsy and biomarker testing, as well as how healthcare professionals can guide new patients through this process.
ONCOLOGY AND THERAPY
(2023)
Article
Oncology
Stephen Liu, Tony S. K. Mok, Barzin Y. Nabet, Aaron S. Mansfield, Richard De Boer, Gyorgy Losonczy, Shunichi Sugawara, Rafal Dziadziuszko, Maciej Krzakowski, Alexey Smolin, Maximilian J. Hochmair, Marina C. Garassino, Carl M. Gay, John Heymach, Lauren A. Byers, Sivuonthanh Lam, Andres Cardona, Stefanie Morris, Leah Adler, David S. Shames, Martin Reck
Summary: In the Phase I/III IMpower133 study, atezolizumab in combination with carboplatin and etoposide demonstrated improved overall survival and progression-free survival for patients with extensive-stage small cell lung cancer. The study also revealed associations between long-term survival and patient and disease characteristics, as well as differential gene expression and SCLC transcriptional subtypes.
Article
Oncology
Xiuning Le, Lingzhi Hong, Chuck Hensel, Rongrong Chen, Haley Kemp, Niamh Coleman, Christine A. Ciunci, Stephen Liu, Marcelo Negrao, Jennifer Yen, Xuefeng Xia, Juergen Scheuenpflug, Christopher Stroh, Dilafruz Juraeva, Anne Tsao, David Hong, Victoria Raymond, Paul Paik, Jianjun Zhang, John Heymach
Summary: METex14 mutations frequently co-occur with other potential driver oncogenes with differing patterns of clonal dominance observed among the drivers. This cellular context can provide insights into whether METex14 is acting as a primary oncogenic driver or resistance mechanism and help guide treatment choices.
JCO PRECISION ONCOLOGY
(2021)